Clinical Trial Finder

Inclusion Criteria:

• - Pts have confirmed diagnosis of GBM & radiographic evidence of recurrence following prior therapy w bev + irinotecan.

• - Age >18 yrs.

• - Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy.

• - Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart, /there is biopsy-proven tumor progression.

• - Interval of >4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.

• - Eastern Cooperative Oncology Group (ECOG) 0-1.

• - Hematocrit >29percent, absolute neutrophil count (ANC)>1,000 cells/ml l, platelets > 100,000 cells/ml l.

• - Serum creatinine<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) & bilirubin<1.5 times upper limit of normal (ULN) - Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry.

• - No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1.

• - If sexually active, pts will take contraceptive measures for duration of treatments.

Exclusion Criteria:

• - Co-medication that may interfere w study results.

• - Active infection requiring intravenous antibiotics.

• - Progression to daily etoposide/progression to daily temo.

• - Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide.

• - Requires therapeutic anti-coagulation with warfarin.

• - Inability to comply w study and/or follow-up procedures.

• - Current, recent,/planned participation in experimental drug study other than Genentech-sponsored bev cancer study.

• - Inadequately controlled hypertension.

• - Any prior history of hypertensive crisis/hypertensive encephalopathy.

• - New York Heart Association (NYHA) Gr II/greater congestive heart failure.

• - History of myocardial infarction (MI)/unstable angina within 6 mths prior to study enrollment.

• - History of stroke/transient ischemic attack within 6 mths prior to study enrollment.

• - Significant vascular disease.

• - Symptomatic peripheral vascular disease.

• - Evidence of bleeding diathesis or coagulopathy.

• - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.

• - Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.

• - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.

• - Serious, non-healing wound, ulcer, or bone fracture.

• - Proteinuria at screening as demonstrated by either: - urine protein:creatinine (UPC) ratio >1.0 at screening / - Urine dipstick for proteinuria ≥ 2+ - Known hypersensitivity to any component of bevacizumab.

• - Pregnant or lactating.

Use of effective means of contraception in subjects of child-bearing potential

This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide & approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM & radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I & II error rates associated w testing are 0.030 & 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, & bev.

Arms

Experimental: Temo + Avastin

Patients treated with bevacizumab + temozolomide

Experimental: VP-16 + Avastin

Patients treated with bevacizumab and VP-16 (etoposide)

Interventions

Drug: - Temo + Avastin

Patients have progressed/had gr3/> toxicity related to etoposide, with no had progression/gr 3/> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.

Drug: - VP-16 + Avastin

Patients have progressed/had gr3/> toxicity related to temozolomide, but have not progressed/gr3/> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.